Abstract
Members of the transforming growth factor-beta (TGF-beta) superfamily, including TGF-beta, bone morphogenetic proteins (BMPs), activins and nodals, are vital for regulating growth and differentiation. These growth factors transduce their signals through pairs of transmembrane type I and type II receptor kinases. Here, we have cloned a transmembrane protein, BAMBI, which is related to TGF-beta-family type I receptors but lacks an intracellular kinase domain. We show that BAMBI is co-expressed with the ventralizing morphogen BMP4 (refs 5, 6) during Xenopus embryogenesis and that it requires BMP signalling for its expression. The protein stably associates with TGF-beta-family receptors and inhibits BMP and activin as well as TGF-beta signalling. Finally, we provide evidence that BAMBI's inhibitory effects are mediated by its intracellular domain, which resembles the homodimerization interface of a type I receptor and prevents the formation of receptor complexes. The results indicate that BAMBI negatively regulates TGF-beta-family signalling by a regulatory mechanism involving the interaction of signalling receptors with a pseudoreceptor.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Activins
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Amino Acid Sequence
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Animals
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Protein Receptors, Type I
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Bone Morphogenetic Proteins / antagonists & inhibitors
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Bone Morphogenetic Proteins / metabolism
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COS Cells
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Culture Techniques
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Embryo, Nonmammalian / metabolism
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Gene Expression
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Humans
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Inhibins / antagonists & inhibitors
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Inhibins / metabolism
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Ligands
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Membrane Proteins / chemistry
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Mice
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Molecular Sequence Data
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Protein Serine-Threonine Kinases / chemistry
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Receptors, Growth Factor / chemistry
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Receptors, Transforming Growth Factor beta / metabolism
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Sequence Homology
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Signal Transduction*
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Transforming Growth Factor beta / metabolism*
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Tumor Cells, Cultured
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Xenopus
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Xenopus Proteins*
Substances
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BAMBI protein, human
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BMP4 protein, human
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Bambi protein, mouse
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Bmp4 protein, mouse
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Bone Morphogenetic Protein 4
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Bone Morphogenetic Proteins
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Ligands
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Membrane Proteins
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Receptors, Growth Factor
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Receptors, Transforming Growth Factor beta
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Transforming Growth Factor beta
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Xenopus Proteins
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bambi-A protein, Xenopus
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bmp4 protein, Xenopus
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Activins
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Inhibins
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Protein Serine-Threonine Kinases
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Bone Morphogenetic Protein Receptors, Type I